Carcinogenesis lecture: Flashcards
Proto-oncogenes are involved in regulationof what?
cell proliferation (mitosis)
Define promotion, is it reversible or irreversible?
Initiated cells that dividing like crazy and forms a focal lesion. Promotion is reversible!
Tumor:
Lesion characterized by swelling or increase in size, may or may not be neoplastic
Metastases:
Secondary growths derived from a primary malignant neoplasm
what are 4 examples of metals that are carcinogens?
- Arsenic
- Nickels
- Chromium
- Cadmium
define progression, is it reversible or irreversible?
Progression of this focal lesion to this malignant neoplasia/tumor. Extremely evil cells that lots of weird stuff happens. This is irreversible
Neoplasia:
new growth or autonomous growth of tissue
Cancer:
Malignant neoplasm
Nongenotixic:
Carcinogens that modify gene expression but do not damage DNA
Define group 2b: Evidence for group 2b:
Agent is possibly carcinogenic to humans
Human epidemiological data is weak Animal data positive
what are the 5 categories of carcinogens?
- Genotoxic carcinogens
- Non-genotoxic carcinogens (epigenetics)
- Cocarcinogens
- Solid state carcinogens
- Metals
Benign:
Lesions characterized by expansive growth, frequently exhibiting slow rates of proliferation that do not invade surrounding tissues
Carcinogen:
A physical or chemical agent that causes or induces neoplasia
define complete carcinogens: and provide an example.
involved in all three stages! Initiation, promotion and progression! ex.) tobacco smoke
Describe the happy and sad pathways of this image:
The bioactivation is what makes those silly epoxides.
:): this reactive metabolite can interact wityh GSH and detoxify it!
:(: The ultimate carcinogen binds with DNA and causes alteration with that DNA which is now called bulky DNA.
:): This bulky DNA can be repaired by nuceltoide excision repair
:(: but if it was to continue on and that mutation is retained genetically, this really sucks when it activated the tumor supressor genes or proto-oncogenes
what is an example of a tumor suppressor gene mutation that results in about half of human cancers?
p53
Define group 3: Evidence for group 3:
Agent is not classifiable as to carcinogenicity to humans. Human and animal data inadequate
what is Aflatoxin B1-
fungal metabolite in improperly stores foods. Used to study carcinogenesis because we know they cause cancer. Also an example of a procarcinogen tirned into an ultimate carcinogen
Define group 4: Evidence for group 4:
Agent is probably not carcinogenic to humans Human and animal data negative
give an example of a procarcinogen turned into ultimate carcinogen:
PAHs (polycyclic aromatic hydrocarbons)- Can be activated by CYP to produce this epoxide. Irreversible effects so you need DNA repair to clip it out. When you damage a specific portion of the DNA like the pronco-oncogenes or tumor suppressor genes thats when cancer occurs.
Neoplasm:
the lesion resulting from the neoplasia
what are the malfunctions of various repair/protective processes that can result in cancer:
- Failure of DNA repair 2. Failure of apoptosis 3. Failure to terminate cell proliferation
describe solid state carcinogens and give 2 examples?
Does not interact with DNA but there is constant irritation. Fine particles in alveoli just cause constant irritation and stimulate proliferation and you end up with a rare form of cancer.
ex.) asbestos, silica
is initiation reversible or irreversible?
irreversible
Describe genotoxic carcinogens?
Most concering, this produces metabolites that can damage DNA and if that region of DNA is related to proto-oncogenes or tumor supressor genes, that is what leads to at least half of all human cancers!
how many types of cancer are there?
>200
what are the 3 distinct stages of carcinogenesis:
- Initiaion 2. Promotion 3. Progression
define non-genotoxic (epigenetic) carcinogens:
stimulators of mitosis and/or inhibitors of apoptosis. But it does not damage DNA.
2 examples of cocarcinogens?
ethanol and asbestos
Cancer is a complex. ————– disease
multifactorial
define procarcinogens and ultimate carcinogens:
Although some xenobitoics are direct-acting , most carcinogenic chemicals are inactive (called procarcinogens) and must be bioactivated to yield reactive metabolites such as epoxides (called ultimate carcinogens)
whats the role of P53?
In normal cells, the damage can be repaired or the cell is pushed into apoptosis. However, in cells with mutatedt P53, reuslting in lack of p53 function, this control mechanism is no longer operating and the cell undergoes uncontrolled proliferation.
Define group 1: Evidence for group 1:
Agent is carcinogenic to humans Human data is strong Animal data is strong
what are 4 examples of promoters?
- Xenobitoics 2. Hormones 3. Caloric intake 4. Ethanol
Genotoxic:
Carcinogens that interact with DNA resulting in mutation
Evidence for cancer-causing chemicals comes from 2 places, what are they?
- Human data (usually epidemiological) 2. Lab animals (dose-response experiments)
define co-carcinogens?
Not carcinogenic but increase effect of carcinoens. It potentiates the effect of a carcinogen. Mainly involved in ADME.
Malignant:
Lesions demonstrating invasive growth, capable of metastases to other tissues and organs
Tumor supressor genes are playfully termed what?
guardians of the genome
describe 2 examples of non-genotoxic (epigenetic) carcinogens?
DDT- mitogens
Endogenous mitogens- hormones, growth factors
Define group 2a: Evidence for group 2a:
Agent is probably carcinogenic to humans Human epidemiology data suggestive Animal data positive
what are the two ways in which initiation can occur?
- Neoplasia- proto-oncogenes –> oncogenes. This occurs through a mutations and that mutations is caused through DNA damage 2. Tumor suppressor genes- these are cells that initiate cells to die. They get mutated as well and fail to stop mitosis.
